Studies on carcinoembryonic antigen (CEA) have been pursued in man, rat and mouse. Enzyme-linked immunosorbent assay (ELISA) was refined to the point where it has the sensitivity of 100 ng/ml and may be employed for diagnostic purposes to replace radioimmunoassay. After having identified the CEA-like antigen in transplantable colonic adenocarcinoma of rat and mouse by means of rabbit immune sera, we concentrated our efforts on immunization with CEA within the species (significantly, CEA antibodies were never convincingly demonstrated in man). We immunized Fischer rats with RCA-1 tumor, which is a carcinogen-induced colonic carcinoma transplantable in these rats. After immunization with tumor extract incorporated into complete Freund's adjuvant, the rats formed CEA-specific antibodies and showed a very significant degree of resistance to the tumor. Experiments on passive transfer of this resistance by antibody-containing serum are in progress. The possible application of these findings in human trials is obvious. Further studies have been conducted on heterophile antigens and antibodies. These studies led to the clear distinction of two antigenic entities within the Paul-Bunnell (P-B) antigenic complex. Distribution of these antigens in tissue and sera in various diseases has been investigated. It also was shown that infectious mononucleosis sera with false-negative heterophile test are usually missing antibodies to one but not to both antigens of the P-B complex. Studies on heterophile antigens and antibodies of the Hanganutziu-Deicher variety in malignancy and other human diseases have been extensively pursued and a number of related but not identical antigen-antibody systems have been defined.